Nonspecific or postjunctional supersensitivity is a manifestation of the internal adjustment which excitable cells make to compensate for chronic changes in the level of stimulus they receive via their innervation. Work in this project has established that, in the guinea pig vas deferens, changes in resting membrane potential, changes in calcium binding or movement and improved electrical coupling all may contribute to postjunctional sensitivity changes. Work in the coming year will be directed toward (1) further analysis of the electrophysiologic, ionic and morphologic changes in the vas deferens, (2) determining the relative importance of each of these changes in the vas deferens and (3) extension of our investigations to vascular smooth muscle. Measurements to be made include membrane potential, electronic space constant, characteristics of spontaneous and evoked electrical potential, content and uptake of calcium in subcellular fractions, incidence of nexuses in electronmicrographs and dose-response curves with various agonists after induction of supersensitivity by denervation, decentralization or chronic administration of reserpine. BIBLIOGRAPHIC REFERENCES: Taylor, D. A. Westfall, D. P., de Moraes, S. and Fleming, W. W.: The effect of pretreatment with reserpine on the diastolic potential of guinea pig atrial cells. Naunyn-Schmiedeberg's Arch. Pharmacol. 293:81-87, 1976. Fleming, W. W.: The variable sensitivity of excitable cells: possible mechanisms and biological significance, Reviews of Neuroscience 2:43-90, 1976.